N¹,N²-bis(7-chloroquinolin-4-yl)pentane-1,5-diamine | 140926-79-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: N¹,N²-bis(7-chloroquinolin-4-yl)pentane-1,5-diamine
• 英文别名: N,N′-bis(7-chloroquinolin-4-yl)pentane-1,5-diamine；N,N'-bis-(7-chloro-[4]quinolyl)-pentanediyldiamine；N,N'-Bis-(7-chlor-[4]chinolyl)-pentandiyldiamin；N,N'-bis(7-chloroquinolin-4-yl)pentane-1,5-diamine
• CAS: 140926-79-0
• 化学式: C₂₃H₂₂Cl₂N₄
• 分子量: 425.36
• InChiKey: JBTFFRGMIAACAO-UHFFFAOYSA-N

物化性质

• 熔点：
  266-267 °C
• 沸点：
  655.1±55.0 °C(Predicted)
• 密度：
  1.340±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.4
• 重原子数：
  29
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  49.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1,5-二碘戊烷 、 N¹,N²-bis(7-chloroquinolin-4-yl)pentane-1,5-diamine 、 三氟乙酸 以 N,N-二甲基甲酰胺 、 水 为溶剂， 反应 48.0h， 以8%的产率得到1⁷,7⁷-dichloro-8,14-diaza-1,7(1,4)-diquinolinacyclotetradecaphanium ditrifluoroacetate sesquihydrate
  参考文献：
  名称：

  关于双电荷四氮杂环烷作为小电导Ca 2+激活的K +通道的强抑制剂的进一步研究

  摘要：

  以前，已证明基于喹啉鎓的四氮杂环烷酮（例如UCL 1684和UCL 1848）作为有效的小肽非肽类阻滞剂，对化学结构的变化（尤其是对环庚烷体系的大小）非常敏感。电导Ca 2+激活的K +离子通道（SK Ca）。当前的工作试图优化UCL 1848中连接链的结构。我们报道了29个UCL 1848类似物的合成和SK Ca通道阻滞活性，其中UCL 1848的中心CH 2被其他基团X或取代。 Y = O，S，CF 2，C O，CHOH，C C，CHCH，CHMe，以探索键长或柔韧性的细微变化是否可以进一步提高效力。通过合成和测试带有取代基（NO 2，NH 2，CF 3，F，Cl，CH 3，OCH 3，OCF 3， OH）在氨基喹啉鎓环的5、6或7个位置上。与我们之前的工作一样，测定了每种化合物对大鼠交感神经元后超极化（AHP）的抑制作用，这种作用是由SK Ca通道的SK3亚型介导的。一种新化合物（39，R

  DOI：

  10.1016/j.ejmech.2013.02.029
• 作为产物：
  描述：

  4,7-二氯喹啉 、 1,5-二氨基戊烷 在 三乙胺 作用下， 以 various solvent(s) 为溶剂， 以50%的产率得到N¹,N²-bis(7-chloroquinolin-4-yl)pentane-1,5-diamine
  参考文献：
  名称：

  Bisquinolines. 1. N,N-bis(7-chloroquinolin-4-yl)alkanediamines with potential against chloroquine-resistant malaria

  摘要：

  On the basis of observations that several bisquinolines such as piperaquine possess notable activity against chloroquine-resistant malaria, 13 N,N-bis-(7-chloroquinolin-4-yl)alkanediamines were synthesized and screened against Plasmodium falciparum in vitro and Plasmodium berghei in vivo. Twelve of the thirteen bisquinolines had a significantly lower resistance index than did chloroquine; the resistance index was apparently unrelated to either in vitro or in vivo activity. Except for two compounds, there was a reasonable correlation between in vitro and in vivo activities. Seven of the thirteen bisquinolines had IC50's of less than 6 nM against both chloroquine-sensitive (D-6) and -resistant (W-2) clones of P. falciparum and were curative against P. berghei at doses of 640 mg/kg. In contrast to chloroquine, these bisquinolines did not show any toxic deaths at curative dose levels. Four bisquinolines, however, caused skin lesions at the site of injection. Maximum activity was seen in bisquinolines with a connecting bridge of two carbon atoms where decreased conformational mobility seemed to increase activity. Bisquinoline 3 ((+/-)-trans-N1,N2-bis(7-chloroquinolin-4-yl)cyclohexane-1,2-diamine was not only the most potent bisquinoline in vitro, but was clearly unique in its in vivo activity-80% and 100% cure rates were achieved at doses of 160 and 320 mg/kg, respectively. In summary, these preliminary results support the premise that bisquinolines may be useful agents against chloroquine-resistant malaria.

  DOI：

  10.1021/jm00089a025

文献信息

• US2816893
  申请人：——

  公开号：——

  公开（公告）日：——
• NOVEL BISAMINOQUINOLINE COMPOUNDS, PHARMACEUTICAL COMPOSITIONS PREPARED THEREFROM AND THEIR USE
  申请人：Amaravadi Ravi K.

  公开号：US20140050696A1

  公开（公告）日：2014-02-20

  The present invention relates to novel bisaminoquinoline compounds, pharmaceutical compositions comprising these novel compounds and methods for inhibiting autophagy in biological systems. Methods of treating cancer in patients in need using compounds and/or compositions according to the present invention alone or in combination with at least one additional anticancer agent represent additional aspects of the invention. Methods of treating disease states and/or conditions in which inhibition of autophagy plays a favorable treatment role including rheumatoid arthritis, malaria, antiphospholipid antibody syndrome, lupus, chronic urticaria and Sjogren's disease, with compounds according to the present invention represent additional aspects of the invention.